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1
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Zhang L, Swaab DF. Sex differences in bipolar disorder: The dorsolateral prefrontal cortex as an etiopathogenic region. Front Neuroendocrinol 2024; 72:101115. [PMID: 37993020 DOI: 10.1016/j.yfrne.2023.101115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 11/15/2023] [Accepted: 11/19/2023] [Indexed: 11/24/2023]
Abstract
Bipolar disorder (BD) is worldwide a prevalent mental illness and a leading risk factor for suicide. Over the past three decades, it has been discovered that sex differences exist throughout the entire panorama of BD, but the etiologic regions and mechanisms that generate such differences remain poorly characterized. Available evidence indicates that the dorsolateral prefrontal cortex (DLPFC), a critical region that controls higher-order cognitive processing and mood, exhibits biological disparities between male and female patients with psychiatric disorders, which are highly correlated with the co-occurrence of psychotic symptoms. This review addresses the sex differences in BD concerning epidemiology, cognitive impairments, clinical manifestations, neuroimaging, and laboratory abnormalities. It also provides strong evidence linking DLPFC to the etiopathogenesis of these sex differences. We emphasize the importance of identifying gene signatures using human brain transcriptomics, which can depict sexually different variations, explain sex-biased symptomatic features, and provide novel targets for sex-specific therapeutics.
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Affiliation(s)
- Lin Zhang
- Neuropsychiatric Disorders Lab, Neuroimmunology Group, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands
| | - Dick F Swaab
- Neuropsychiatric Disorders Lab, Neuroimmunology Group, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands.
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2
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Mas-Bermejo P, Papiol S, Via M, Rovira P, Torrecilla P, Kwapil TR, Barrantes-Vidal N, Rosa A. Schizophrenia polygenic risk score in psychosis proneness. Eur Arch Psychiatry Clin Neurosci 2023; 273:1665-1675. [PMID: 37301774 PMCID: PMC10713704 DOI: 10.1007/s00406-023-01633-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 05/29/2023] [Indexed: 06/12/2023]
Abstract
Schizophrenia (SZ) is a complex disorder with a highly polygenic inheritance. It can be conceived as the extreme expression of a continuum of traits that are present in the general population often broadly referred to as schizotypy. However, it is still poorly understood how these traits overlap genetically with the disorder. We investigated whether polygenic risk for SZ is associated with these disorder-related phenotypes (schizotypy, psychotic-like experiences, and subclinical psychopathology) in a sample of 253 non-clinically identified participants. Polygenic risk scores (PRSs) were constructed based on the latest SZ genome-wide association study using the PRS-CS method. Their association with self-report and interview measures of SZ-related traits was tested. No association with either schizotypy or psychotic-like experiences was found. However, we identified a significant association with the Motor Change subscale of the Comprehensive Assessment of At-Risk Mental States (CAARMS) interview. Our results indicate that the genetic overlap of SZ with schizotypy and psychotic-like experiences is less robust than previously hypothesized. The relationship between high PRS for SZ and motor abnormalities could reflect neurodevelopmental processes associated with psychosis proneness and SZ.
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Affiliation(s)
- Patricia Mas-Bermejo
- Secció de Zoologia i Antropologia Biològica. Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals. Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 643, 08028, Barcelona, Spain
- Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain
| | - Sergi Papiol
- Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, 80336, Munich, Germany
- Max Planck Institute of Psychiatry, Munich, Germany
- CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain
| | - Marc Via
- Brainlab, Cognitive Neuroscience Research Group, Department of Clinical Psychology and Psychobiology, Universitat de Barcelona, Barcelona, Spain
- Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain
- Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Spain
| | - Paula Rovira
- Vicerectorat de Recerca, Investigadora Postdoctoral Margarita Salas, Universitat de Barcelona, Barcelona, Spain
- Instituto de Neurociencias, Centro de Investigación Biomédica (CIBM), Universidad de Granada, Granada, Spain
- Departamento de Psiquiatría, Facultad de Medicina, Universidad de Granada, Granada, Spain
- Instituto de Investigación Biosanitaria Ibs.Granada, Granada, Spain
| | - Pilar Torrecilla
- Department of Clinical and Health Psychology, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Thomas R Kwapil
- Department of Psychology, University of Illinois at Urbana-Champaign, Champaign, IL, USA
| | - Neus Barrantes-Vidal
- CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain
- Department of Clinical and Health Psychology, Universitat Autònoma de Barcelona, Barcelona, Spain
- Sant Pere Claver-Fundació Sanitària, Barcelona, Spain
| | - Araceli Rosa
- Secció de Zoologia i Antropologia Biològica. Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals. Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 643, 08028, Barcelona, Spain.
- Institut de Biomedicina de la Universitat de Barcelona, Barcelona, Spain.
- CIBER de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain.
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3
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Zhang X, Lee J, Goh WWB. An Investigation of How Normalisation and Local Modelling Techniques Confound Machine Learning Performance In a Mental Health Study. Heliyon 2022; 8:e09502. [PMID: 35663731 PMCID: PMC9156999 DOI: 10.1016/j.heliyon.2022.e09502] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 03/12/2022] [Accepted: 05/16/2022] [Indexed: 01/12/2023] Open
Abstract
Machine learning (ML) is increasingly deployed on biomedical studies for biomarker development (feature selection) and diagnostic/prognostic technologies (classification). While different ML techniques produce different feature sets and classification performances, less understood is how upstream data processing methods (e.g., normalisation) impact downstream analyses. Using a clinical mental health dataset, we investigated the impact of different normalisation techniques on classification model performance. Gene Fuzzy Scoring (GFS), an in-house developed normalisation technique, is compared against widely used normalisation methods such as global quantile normalisation, class-specific quantile normalisation and surrogate variable analysis. We report that choice of normalisation technique has strong influence on feature selection. with GFS outperforming other techniques. Although GFS parameters are tuneable, good classification model performance (ROC-AUC > 0.90) is observed regardless of the GFS parameter settings. We also contrasted our results against local modelling, which is meant to improve the resolution and meaningfulness of classification models built on heterogeneous data. Local models, when derived from non-biologically meaningful subpopulations, perform worse than global models. A deep dive however, revealed that the factors driving cluster formation has little to do with the phenotype-of-interest. This finding is critical, as local models are often seen as a superior means of clinical data modelling. We advise against such naivete. Additionally, we have developed a combinatorial reasoning approach using both global and local paradigms: This helped reveal potential data quality issues or underlying factors causing data heterogeneity that are often overlooked. It also assists to explain the model as well as provides directions for further improvement.
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Affiliation(s)
- Xinxin Zhang
- School of Biological Sciences, Nanyang Technological University, 637551, Singapore
| | - Jimmy Lee
- North Region & Department of Psychosis, Institute of Mental Health, 539747, Singapore
- Corresponding author.
| | - Wilson Wen Bin Goh
- School of Biological Sciences, Nanyang Technological University, 637551, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, 636921, Singapore
- Centre for Biomedical Informatics, Nanyang Technological University, 636921, Singapore
- Corresponding author.
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4
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Zmijewski P, Leońska-Duniec A, Stuła A, Sawczuk M. Evaluation of the Association of COMT Rs4680 Polymorphism with Swimmers' Competitive Performance. Genes (Basel) 2021; 12:1641. [PMID: 34681035 PMCID: PMC8535192 DOI: 10.3390/genes12101641] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 10/12/2021] [Accepted: 10/14/2021] [Indexed: 12/24/2022] Open
Abstract
Swimmers' competitive performance is a result of complicated interactions between physiological, biochemical, physical and psychological factors, all of which are strongly affected by water. Recently, great attention has been paid to the role of genetic factors such as the catechol-O-methyltransferase gene (COMT) influencing motivation, emotions, stress tolerance, self-control, sleep regulation, pain processing and perception, addictive behaviour and neurodegeneration, which may underlie differences in achieving remarkable results in sports competition. Thus, this study was performed to investigate the association between the COMT Val158Met (rs4680) polymorphism and athletic performance in Caucasian swimmers. A total of 225 swimmers (171 short distance (SDS) and 54 long distance swimmers (LDS)) of national or international competitive standard and 379 unrelated sedentary controls were genotyped using real-time polymerase chain reaction (real-time PCR). We found no significant differences in genotypic or allelic distributions between (1) male and female athletes; (2) SDS and LDS; (3) all athletes and sedentary controls (under codominant, dominant, recessive, and overdominant genetic models). No association was found between the COMT rs4680 polymorphism and elite swimming athlete status of the studied population. However, more replication studies are needed.
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Affiliation(s)
- Piotr Zmijewski
- Faculty of Physical Education, Jozef Pilsudski University of Physical Education in Warsaw, 00-809 Warsaw, Poland
| | - Agata Leońska-Duniec
- Faculty of Physical Education, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland;
| | - Aleksander Stuła
- Department of Physical Education and Physiotherapy, Opole University of Technology, 45-758 Opole, Poland;
| | - Marek Sawczuk
- Institute of Physical Culture Sciences, University of Szczecin, 70-453 Szczecin, Poland;
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5
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Elek Z, Rónai Z, Hargitai R, Réthelyi J, Arndt B, Matuz A, Csathó Á, Polner B, Kállai J. Magical thinking as a bio-psychological developmental disposition for cognitive and affective symptoms intensity in schizotypy: Traits and genetic associations. PERSONALITY AND INDIVIDUAL DIFFERENCES 2021. [DOI: 10.1016/j.paid.2020.110498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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6
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Xia Y, Dai R, Wang K, Jiao C, Zhang C, Xu Y, Li H, Jing X, Chen Y, Jiang Y, Kopp RF, Giase G, Chen C, Liu C. Sex-differential DNA methylation and associated regulation networks in human brain implicated in the sex-biased risks of psychiatric disorders. Mol Psychiatry 2021; 26:835-848. [PMID: 30976086 PMCID: PMC6788945 DOI: 10.1038/s41380-019-0416-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 03/18/2019] [Accepted: 03/22/2019] [Indexed: 01/29/2023]
Abstract
Many psychiatric disorders are characterized by a strong sex difference, but the mechanisms behind sex-bias are not fully understood. DNA methylation plays important roles in regulating gene expression, ultimately impacting sexually different characteristics of the human brain. Most previous literature focused on DNA methylation alone without considering the regulatory network and its contribution to sex-bias of psychiatric disorders. Since DNA methylation acts in a complex regulatory network to connect genetic and environmental factors with high-order brain functions, we investigated the regulatory networks associated with different DNA methylation and assessed their contribution to the risks of psychiatric disorders. We compiled data from 1408 postmortem brain samples in 3 collections to identify sex-differentially methylated positions (DMPs) and regions (DMRs). We identified and replicated thousands of DMPs and DMRs. The DMR genes were enriched in neuronal related pathways. We extended the regulatory networks related to sex-differential methylation and psychiatric disorders by integrating methylation quantitative trait loci (meQTLs), gene expression, and protein-protein interaction data. We observed significant enrichment of sex-associated genes in psychiatric disorder-associated gene sets. We prioritized 2080 genes that were sex-biased and associated with psychiatric disorders, such as NRXN1, NRXN2, NRXN3, FDE4A, and SHANK2. These genes are enriched in synapse-related pathways and signaling pathways, suggesting that sex-differential genes of these neuronal pathways may cause the sex-bias of psychiatric disorders.
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Affiliation(s)
- Yan Xia
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
- Department of Psychiatry, State University of New York Upstate Medical University, Syracuse, NY, USA
| | - Rujia Dai
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
- Department of Psychiatry, State University of New York Upstate Medical University, Syracuse, NY, USA
| | - Kangli Wang
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
| | - Chuan Jiao
- Department of Psychiatry, State University of New York Upstate Medical University, Syracuse, NY, USA
| | - Chunling Zhang
- Department of Neuroscience, State University of New York Upstate Medical University, Syracuse, NY, USA
| | - Yuchen Xu
- Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Honglei Li
- Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Xi Jing
- Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Yu Chen
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
| | - Yi Jiang
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China
- Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Richard F Kopp
- Department of Psychiatry, State University of New York Upstate Medical University, Syracuse, NY, USA
| | - Gina Giase
- Department of Public Health, University of Illinois at Chicago, Chicago, IL, USA
| | - Chao Chen
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
- Department of Psychiatry, State University of New York Upstate Medical University, Syracuse, NY, USA.
- National Clinical Research Center for Geriatric Disorders, the Xiangya Hospital, Central South University, Changsha, Hunan, China.
| | - Chunyu Liu
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
- Department of Psychiatry, State University of New York Upstate Medical University, Syracuse, NY, USA.
- School of Psychology, Shaanxi Normal University, Xi'an, China.
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7
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Seiler N, Nguyen T, Yung A, O'Donoghue B. Terminology and assessment tools of psychosis: A systematic narrative review. Psychiatry Clin Neurosci 2020; 74:226-246. [PMID: 31846133 DOI: 10.1111/pcn.12966] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Accepted: 12/05/2019] [Indexed: 12/20/2022]
Abstract
AIM Phenomena within the psychosis continuum that varies in frequency/duration/intensity have been increasingly identified. Different terms describe these phenomena, however there is no standardization within the terminology. This review evaluated the definitions and assessment tools of seven terms - (i) 'psychotic experiences'; (ii) 'psychotic-like experiences'; (iii) 'psychotic-like symptoms'; (iv) 'attenuated psychotic symptoms'; (v) 'prodromal psychotic symptoms'; (vi) 'psychotic symptomatology'; and (vii) 'psychotic symptoms'. METHODS EMBASE, MEDLINE, and CINAHL were searched during February-March 2019. Inclusion criteria included 1989-2019, full text, human, and English. Papers with no explicit definition or assessment tool, duplicates, conference abstracts, systematic reviews, meta-analyses, or no access were excluded. RESULTS A total of 2238 papers were identified and of these, 627 were included. Definitions and assessment tools varied, but some trends were found. Psychotic experiences and psychotic-like experiences were transient and mild, found in the general population and those at-risk. Psychotic-like symptoms were subthreshold and among at-risk populations and non-psychotic mental disorders. Attenuated psychotic symptoms were subthreshold but associated with distress, risk, and help-seeking. Prodromal psychotic symptoms referred to the prodrome of psychotic disorders. Psychotic symptomatology included delusions and hallucinations within psychotic disorders. Psychotic symptoms was the broadest term, encompassing a range of populations but most commonly involving hallucinations, delusions, thought disorder, and disorganization. DISCUSSION A model for conceptualizing the required terms is proposed and future directions needed to advance this field of research are discussed.
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Affiliation(s)
- Natalie Seiler
- Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Melbourne, Australia.,Centre for Youth Mental Health, University of Melbourne, Parkville, Melbourne, Australia.,The University of Melbourne, Parkville, Melbourne, Australia.,Orygen Youth Health, Parkville, Melbourne, Australia
| | - Tony Nguyen
- Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Melbourne, Australia.,Centre for Youth Mental Health, University of Melbourne, Parkville, Melbourne, Australia.,The University of Melbourne, Parkville, Melbourne, Australia.,Orygen Youth Health, Parkville, Melbourne, Australia
| | - Alison Yung
- Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Melbourne, Australia.,Centre for Youth Mental Health, University of Melbourne, Parkville, Melbourne, Australia.,Orygen Youth Health, Parkville, Melbourne, Australia
| | - Brian O'Donoghue
- Orygen, the National Centre of Excellence in Youth Mental Health, Parkville, Melbourne, Australia.,Centre for Youth Mental Health, University of Melbourne, Parkville, Melbourne, Australia.,Orygen Youth Health, Parkville, Melbourne, Australia
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8
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Sagud M, Tudor L, Uzun S, Perkovic MN, Zivkovic M, Konjevod M, Kozumplik O, Vuksan Cusa B, Svob Strac D, Rados I, Mimica N, Mihaljevic Peles A, Nedic Erjavec G, Pivac N. Haplotypic and Genotypic Association of Catechol- O-Methyltransferase rs4680 and rs4818 Polymorphisms and Treatment Resistance in Schizophrenia. Front Pharmacol 2018; 9:705. [PMID: 30018555 PMCID: PMC6037851 DOI: 10.3389/fphar.2018.00705] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 06/11/2018] [Indexed: 12/12/2022] Open
Abstract
Treatment-resistant schizophrenia (TRS) continues to be a challenge. It was related to different factors, including alterations in the activity of brain dopaminergic system, which could be influenced by the dopamine-degrading enzyme, catechol-O-methyltransferase (COMT). Variants of the COMT gene have been extensively studied as risk factors for schizophrenia; however, their association with TRS has been poorly investigated. The aim of the present study was to determine the haplotypic and genotypic association of COMT rs4680 and rs4818 polymorphisms with the presence of TRS. Overall, 931 Caucasian patients diagnosed with schizophrenia (386 females and 545 males) were included, while 270 participants met the criteria for TRS. In males, no significant haplotypic and genotypic associations between COMT rs4680 and rs4818 polymorphisms and TRS were detected. However, genotypic analyses demonstrated higher frequency of COMT rs4680 AA genotype carriers compared to G-allele carriers (p = 0.033) and higher frequency of COMT rs4818 CC genotype carriers than G-allele carriers (p = 0.014) in females with TRS. Haplotype analyses confirmed that the presence of the G allele in females was associated with lower risk of TRS. In women with TRS, the high activity G-G/G-G haplotype was rare, while carriers of other haplotypes were overrepresented (p = 0.009). Such associations of COMT rs4680 and rs4818 high-activity (G variants), as well as G-G/G-G haplotype, with the lower risk of TRS in females, but not in males, suggest significant, but sex-specific influence of COMT variants on the development of treatment-resistance in patients with schizophrenia. However, due to relatively low number of females, those findings require replication in a larger sample.
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Affiliation(s)
- Marina Sagud
- School of Medicine, University of Zagreb, Zagreb, Croatia.,Department of Psychiatry, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Lucija Tudor
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia
| | - Suzana Uzun
- Department of Biological Psychiatry and Psychogeriatrics, University Psychiatric Hospital Vrapce, Zagreb, Croatia.,School of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Matea Nikolac Perkovic
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia
| | - Maja Zivkovic
- Department of Integrative Psychiatry, University Psychiatric Hospital Vrapce, Zagreb, Croatia
| | - Marcela Konjevod
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia
| | - Oliver Kozumplik
- Department of Biological Psychiatry and Psychogeriatrics, University Psychiatric Hospital Vrapce, Zagreb, Croatia.,School of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia
| | - Bjanka Vuksan Cusa
- School of Medicine, University of Zagreb, Zagreb, Croatia.,Department of Psychiatry, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Dubravka Svob Strac
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia
| | - Iva Rados
- Department of Psychological Medicine, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Ninoslav Mimica
- School of Medicine, University of Zagreb, Zagreb, Croatia.,Department of Biological Psychiatry and Psychogeriatrics, University Psychiatric Hospital Vrapce, Zagreb, Croatia
| | - Alma Mihaljevic Peles
- School of Medicine, University of Zagreb, Zagreb, Croatia.,Department of Psychiatry, University Hospital Centre Zagreb, Zagreb, Croatia
| | - Gordana Nedic Erjavec
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia
| | - Nela Pivac
- Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia
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9
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Kwapil TR, Gross GM, Silvia PJ, Raulin ML, Barrantes-Vidal N. Development and psychometric properties of the Multidimensional Schizotypy Scale: A new measure for assessing positive, negative, and disorganized schizotypy. Schizophr Res 2018; 193:209-217. [PMID: 28735642 DOI: 10.1016/j.schres.2017.07.001] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Revised: 06/30/2017] [Accepted: 07/01/2017] [Indexed: 01/05/2023]
Abstract
This article reports on the development of a new self-report questionnaire measure of schizotypy - the Multidimensional Schizotypy Scale (MSS). Schizotypy offers a useful and unifying construct for understanding schizophrenia-spectrum psychopathology. Questionnaire measures have been widely used to assess schizotypy and have greatly informed our understanding of the construct. However, available measures suffer from a number of limitations, including lack of a clear conceptual framework, outdated wording, unclear factor structure, and psychometric shortcomings. The MSS is based on current conceptual models and taps positive, negative, and disorganized dimensions of schizotypy. The derivation sample included 6265 participants sampled from four universities and Amazon Mechanical Turk. A separate sample of 1000 participants from these sources was used to examine the psychometric properties of the final subscales. Scale development employed classical test theory, item response theory, and differential item function methods. The positive schizotypy and negative schizotypy subscales contain 26 items each, and the disorganized schizotypy subscale contains 25 items. The psychometric properties were almost identical in the derivation and validation samples. All three subscales demonstrated good to excellent reliability, high item-scale correlations, and good item and test curve characteristics. The MSS appears to provide a promising measure for assessing schizotypy.
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Affiliation(s)
- Thomas R Kwapil
- University of Illinois at Urbana-Champaign, United States; University of North Carolina at Greensboro, United States.
| | | | - Paul J Silvia
- University of North Carolina at Greensboro, United States
| | | | - Neus Barrantes-Vidal
- University of North Carolina at Greensboro, United States; Departament de Psicologia Clínica i de la Salut, Universitat Autònoma de Barcelona, Spain; Sant Pere Claver - Fundació Sanitària, Spain; CIBERSAM, Instituto de Salud Carlos III, Spain
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10
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de Castro-Catala M, Peña E, Kwapil TR, Papiol S, Sheinbaum T, Cristóbal-Narváez P, Ballespí S, Barrantes-Vidal N, Rosa A. Interaction between FKBP5 gene and childhood trauma on psychosis, depression and anxiety symptoms in a non-clinical sample. Psychoneuroendocrinology 2017; 85:200-209. [PMID: 28889074 DOI: 10.1016/j.psyneuen.2017.08.024] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Revised: 08/17/2017] [Accepted: 08/22/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Childhood trauma has been associated with a heightened risk for presenting clinical and non-clinical psychopathology in adulthood. Genes related with the stress response, such as the FK506 binding protein 51 (FKBP5), are plausible candidates moderating the effects of childhood trauma on the emergence of such symptoms later on. The present study aimed to explore the moderating role of FKBP5 genetic variability on the association of different types of childhood trauma with subclinical psychosis, depression and anxiety in a non-clinical sample. METHODS Schizotypy, psychotic-like experiences, depression and anxiety symptoms and childhood trauma were assessed in 808 young adults. Two FKBP5 haplotypic blocks were detected: block 1 (rs3800373 - rs9296158 - rs1360780) and block 2 (rs9470080 - rs4713916). Subjects were classified in two groups according to whether they carried or not the risk haplotype previously described in the literature (block 1: CAT and block 2: TA). Linear regression analyses were used to study (i) the main effects of childhood trauma and FKBP5 haplotype blocks and (ii) their interaction effects on the mentioned forms of psychopathology. RESULTS All childhood trauma scales, except sexual abuse, were associated with schizotypy, psychotic-like experiences, depression and anxiety symptoms. None of the analysed symptoms was associated with the main effects of FKBP5 genetic variability. However an interaction effect between block 1 and physical abuse was observed on anxiety, with lower scores in CAT carriers. This effect was driven by SNP 1 and 2. Moreover, an interaction effect between block 2 and physical abuse was identified on the variables tapping depressive and anxiety symptoms. Specifically, non-TA carrier subjects who were exposed to physical abuse were found to be at higher risk for depressive and anxiety symptoms. These effects were driven by SNP 5. No interaction effect was observed for the other variables. CONCLUSIONS Our data suggest that exposure to childhood physical abuse may increase the risk for sub-clinical depressive and anxiety symptoms depending on FKBP5 genetic variability. Further research is needed to better elucidate the role of FKBP5 on mental health in clinical and non-clinical cohorts.
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Affiliation(s)
- Marta de Castro-Catala
- Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Universitat de Barcelona (UB), Avinguda Diagonal 643, 08028 Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain
| | - Elionora Peña
- Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Universitat de Barcelona (UB), Avinguda Diagonal 643, 08028 Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain
| | - Thomas R Kwapil
- Department of Psychology, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, United States; Department of Psychology, University of Illinois at Champaign-Urbana, Champaign, IL 61820, United States
| | - Sergi Papiol
- Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Nussbaumstrasse 7, 80336 Munich, Germany; Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Nussbaumstrasse 7, 80336 Munich, Germany; Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto Carlos III, Madrid, Spain
| | - Tamara Sheinbaum
- Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Barcelona, Spain
| | - Paula Cristóbal-Narváez
- Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Barcelona, Spain
| | - Sergi Ballespí
- Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Barcelona, Spain
| | - Neus Barrantes-Vidal
- Department of Psychology, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, United States; Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto Carlos III, Madrid, Spain; Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Barcelona, Spain; Sant Pere Claver-Fundació Sanitària Carrer Vila i Vilà 16, 08004 Barcelona, Spain
| | - Araceli Rosa
- Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Universitat de Barcelona (UB), Avinguda Diagonal 643, 08028 Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain; Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto Carlos III, Madrid, Spain.
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11
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Ortega-Alonso A, Ekelund J, Sarin AP, Miettunen J, Veijola J, Järvelin MR, Hennah W. Genome-Wide Association Study of Psychosis Proneness in the Finnish Population. Schizophr Bull 2017; 43:1304-1314. [PMID: 28525603 PMCID: PMC5737890 DOI: 10.1093/schbul/sbx006] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The current study examined quantitative measures of psychosis proneness in a nonpsychotic population, in order to elucidate their underlying genetic architecture and to observe if there is any commonality to that already detected in the studies of individuals with overt psychotic conditions, such as schizophrenia and bipolar disorder. Heritability, univariate and multivariate genome-wide association (GWAs) tests, including a series of comprehensive gene-based association analyses, were developed in 4269 nonpsychotic persons participating in the Northern Finland Birth Cohort 1966 study with information on the following psychometric measures: Hypomanic Personality, Perceptual Aberration, Physical and Social Anhedonia (also known as Chapman's Schizotypia scales), and Schizoidia scale. Genome-wide genetic data was available for ~9.84 million SNPs. Heritability estimates ranged from 16% to 27%. Phenotypic, genetic and environmental correlations ranged from 0.04-0.43, 0.25-0.73, and 0.12-0.43, respectively. Univariate GWAs tests revealed an intronic SNP (rs12449097) at the TMC7 gene (16p12.3) that significantly associated (P = 3.485 × 10-8) with the hypomanic scale. Bivariate GWAs tests including the hypomanic and physical anhedonia scales suggested a further borderline significant SNP (rs188320715; P-value = 5.261 × 10-8, ~572 kb downstream the ARID1B gene at 6q25.3). Gene-based tests highlighted 20 additional genes of which 5 had previously been associated to schizophrenia and/or bipolar disorder: CSMD1, CCDC141, SLC1A2, CACNA1C, and SNAP25. Altogether the findings explained from 3.7% to 14.1% of the corresponding trait heritability. In conclusion, this study provides preliminary genomic evidence suggesting that qualitatively similar biological factors may underlie different psychosis proneness measures, some of which could further predispose to schizophrenia and bipolar disorder.
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Affiliation(s)
- Alfredo Ortega-Alonso
- Institute for Molecular Medicine Finland-FIMM, Helsinki, Finland,Department of Health, National Institute for Health and Welfare, Helsinki, Finland,To whom correspondence should be addressed; Institute for Molecular Medicine Finland-FIMM, PO Box 20, FI-00014 University of Helsinki, Finland; e-mail:
| | - Jesper Ekelund
- Department of Health, National Institute for Health and Welfare, Helsinki, Finland,Department of Psychiatry, University of Helsinki, Helsinki, Finland,Department of Psychiatry, Vaasa Hospital District, Vaasa, Finland
| | - Antti-Pekka Sarin
- Institute for Molecular Medicine Finland-FIMM, Helsinki, Finland,Department of Health, National Institute for Health and Welfare, Helsinki, Finland,Department of Public Health, University of Helsinki, Helsinki, Finland
| | - Jouko Miettunen
- Center for Life Course Health Research, University of Oulu, Oulu, Finland,Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Juha Veijola
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland,DDepartment of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland,Department of Psychiatry, Oulu University Hospital, Oulu, Finland
| | - Marjo-Riitta Järvelin
- Center for Life Course Health Research, University of Oulu, Oulu, Finland,Department of Epidemiology and Biostatistics, MRC–PHE Centre for Environment & Health, School of Public Health, Imperial College London, London, UK,Biocenter Oulu, University of Oulu, Oulu, Finland,Unit of Primary Care, Oulu University Hospital, Oulu, Finland
| | - William Hennah
- Institute for Molecular Medicine Finland-FIMM, Helsinki, Finland,Department of Health, National Institute for Health and Welfare, Helsinki, Finland
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12
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de Castro-Catala M, Mora-Solano A, Kwapil TR, Cristóbal-Narváez P, Sheinbaum T, Racioppi A, Barrantes-Vidal N, Rosa A. The genome-wide associated candidate gene ZNF804A and psychosis-proneness: Evidence of sex-modulated association. PLoS One 2017; 12:e0185072. [PMID: 28931092 PMCID: PMC5607189 DOI: 10.1371/journal.pone.0185072] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 09/06/2017] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The Zinc finger protein 804A (ZNF804A) is a promising candidate gene for schizophrenia and the broader psychosis phenotype that emerged from genome-wide association studies. It is related to neurodevelopment and associated to severe symptoms of schizophrenia and alterations in brain structure, as well as positive schizotypal personality traits in non-clinical samples. Moreover, a female-specific association has been observed between ZNF804A and schizophrenia. AIM The present study examined the association of two ZNF804A polymorphisms (rs1344706 and rs7597593) with the positive dimension of schizotypy and psychotic-like experiences in a sample of 808 non-clinical subjects. Additionally, we wanted to explore whether the sexual differences reported in schizophrenia are also present in psychosis-proneness. RESULTS Our results showed an association between rs7597593 and both schizotypy and psychotic-like experiences. These associations were driven by females, such those carrying the C allele had higher scores in the positive dimension of both variables compared to TT allele homozygotes. CONCLUSION The findings of the present study support the inclusion of ZNF804 variability in studies of the vulnerability for the development of psychopathology in non-clinical samples and consideration of sex as a moderator of this association.
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Affiliation(s)
- Marta de Castro-Catala
- Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Spain
- Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain
| | - Aurea Mora-Solano
- Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Spain
| | - Thomas R. Kwapil
- Department of Psychology, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America
- Department of Psychology, University of Illinois at Champaign-Urbana, Champaign, Illinois, United States of America
| | - Paula Cristóbal-Narváez
- Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona (UAB), Bellaterra, Barcelona, Spain
| | - Tamara Sheinbaum
- Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona (UAB), Bellaterra, Barcelona, Spain
| | - Anna Racioppi
- Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona (UAB), Bellaterra, Barcelona, Spain
| | - Neus Barrantes-Vidal
- Department of Psychology, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America
- Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona (UAB), Bellaterra, Barcelona, Spain
- Sant Pere Claver - Fundació Sanitària, Barcelona, Spain
- Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Madrid, Spain
| | - Araceli Rosa
- Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Spain
- Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain
- Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), Madrid, Spain
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13
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Association between RGS4 variants and psychotic-like experiences in nonclinical individuals. Eur Arch Psychiatry Clin Neurosci 2017; 267:19-24. [PMID: 26910404 DOI: 10.1007/s00406-016-0676-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Accepted: 01/25/2016] [Indexed: 12/11/2022]
Abstract
The psychosis phenotype is expressed across a continuum known as schizotypy, which ranges from personality variation through subclinical symptoms to severe psychopathology. The study of subclinical manifestations in non-affected individuals minimizes confounding factors associated with the clinical phenotype and facilitates the differentiation of dimension-specific etiological mechanisms. The aim of the present study was to investigate the association between the variation in the regulator of G-protein signaling 4 (RGS4) gene, a putative candidate gene for psychosis previously associated with schizophrenia endophenotypes, and psychotic-like experiences (PLEs). In total, 808 healthy individuals completed the community assessment of psychic experiences (CAPE) to measure positive and negative PLEs and provided a DNA sample. Two RGS4 single-nucleotide polymorphisms (SNPs) (rs951436 [SNP4] and rs2661319 [SNP18]) were genotyped. Analyses of covariance (ANCOVA) were used to explore the association of positive and negative PLEs with RGS4 variation. Our results showed associations of positive and negative PLEs with the two polymorphisms studied: subjects with the T allele (SNP4) and the A allele (SNP18) had higher scores on both the positive and the negative dimensions. Haplotypic analyses supported these results, showing the highest scores in those with the TA haplotype (SNP4-SNP18). The RGS4 variants might exert gene-specific modulating effects on psychosis proneness.
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14
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Genetic Mechanisms Leading to Sex Differences Across Common Diseases and Anthropometric Traits. Genetics 2016; 205:979-992. [PMID: 27974502 DOI: 10.1534/genetics.116.193623] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Accepted: 12/08/2016] [Indexed: 01/10/2023] Open
Abstract
Common diseases often show sex differences in prevalence, onset, symptomology, treatment, or prognosis. Although studies have been performed to evaluate sex differences at specific SNP associations, this work aims to comprehensively survey a number of complex heritable diseases and anthropometric traits. Potential genetically encoded sex differences we investigated include differential genetic liability thresholds or distributions, gene-sex interaction at autosomal loci, major contribution of the X-chromosome, or gene-environment interactions reflected in genes responsive to androgens or estrogens. Finally, we tested the overlap between sex-differential association with anthropometric traits and disease risk. We utilized complementary approaches of assessing GWAS association enrichment and SNP-based heritability estimation to explore explicit sex differences, as well as enrichment in sex-implicated functional categories. We do not find consistent increased genetic load in the lower-prevalence sex, or a disproportionate role for the X-chromosome in disease risk, despite sex-heterogeneity on the X for several traits. We find that all anthropometric traits show less than complete correlation between the genetic contribution to males and females, and find a convincing example of autosome-wide genome-sex interaction in multiple sclerosis (P = 1 × 10-9). We also find some evidence for hormone-responsive gene enrichment, and striking evidence of the contribution of sex-differential anthropometric associations to common disease risk, implying that general mechanisms of sexual dimorphism determining secondary sex characteristics have shared effects on disease risk.
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15
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de Castro-Catala M, van Nierop M, Barrantes-Vidal N, Cristóbal-Narváez P, Sheinbaum T, Kwapil TR, Peña E, Jacobs N, Derom C, Thiery E, van Os J, van Winkel R, Rosa A. Childhood trauma, BDNF Val66Met and subclinical psychotic experiences. Attempt at replication in two independent samples. J Psychiatr Res 2016; 83:121-129. [PMID: 27596955 DOI: 10.1016/j.jpsychires.2016.08.014] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 08/19/2016] [Accepted: 08/19/2016] [Indexed: 02/06/2023]
Abstract
Childhood trauma exposure is a robust environmental risk factor for psychosis. However, not all exposed individuals develop psychotic symptoms later in life. The Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been suggested to moderate the psychosis-inducing effects of childhood trauma in clinical and nonclinical samples. Our study aimed to explore the interaction effect between childhood trauma and the BDNF Val66Met polymorphism on subclinical psychotic experiences (PEs). This was explored in two nonclinical independent samples: an undergraduate and technical-training school student sample (n = 808, sample 1) and a female twin sample (n = 621, sample 2). Results showed that childhood trauma was strongly associated with positive and negative PEs in nonclinical individuals. A BDNF Val66Met x childhood trauma effect on positive PEs was observed in both samples. These results were discordant in terms of risk allele: while in sample 1 Val allele carriers, especially males, were more vulnerable to the effects of childhood trauma regarding PEs, in sample 2 Met carriers presented higher PEs scores when exposed to childhood trauma, compared with Val carriers. Moreover, in sample 2, a significant interaction was also found in relation to negative PEs. Our study partially replicates previous findings and suggests that some individuals are more prone to develop PEs following childhood trauma because of a complex combination of multiple factors. Further studies including genetic, environmental and epigenetic factors may provide insights in this field.
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Affiliation(s)
- Marta de Castro-Catala
- Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain
| | - Martine van Nierop
- KU Leuven, Department of Neuroscience, Research Group Psychiatry, Centre for Contextual Psychiatry, Leuven, Belgium
| | - Neus Barrantes-Vidal
- Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain; Department of Psychology, University of North Carolina at Greensboro, Greensboro, NC, United States; Sant Pere Claver - Fundació Sanitària, Barcelona, Spain; Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
| | - Paula Cristóbal-Narváez
- Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain
| | - Tamara Sheinbaum
- Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain
| | - Thomas R Kwapil
- Department of Psychology, University of North Carolina at Greensboro, Greensboro, NC, United States
| | - Elionora Peña
- Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain
| | - Nele Jacobs
- KU Leuven, Department of Neuroscience, Research Group Psychiatry, Centre for Contextual Psychiatry, Leuven, Belgium; Faculty of Psychology, Open University of the Netherlands, Heerlen, The Netherlands
| | - Catherine Derom
- Centre of Human Genetics, University Hospital Leuven, Department of Human Genetics, Leuven, Belgium
| | - Evert Thiery
- Department of Neurology, Ghent University Hospital, Ghent, Belgium
| | - Jim van Os
- Department of Psychosis Studies, Institute of Psychiatry, King's College London, King's Health Partners, London, United Kingdom; Maastricht University Medical Centre, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht, The Netherlands
| | - Ruud van Winkel
- KU Leuven, Department of Neuroscience, Research Group Psychiatry, Centre for Contextual Psychiatry, Leuven, Belgium; University Psychiatric Center, Katholieke Universiteit Leuven, Belgium
| | - Araceli Rosa
- Secció de Zoologia i Antropologia Biològica, Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain; Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
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16
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Walter EE, Fernandez F, Snelling M, Barkus E. Genetic Consideration of Schizotypal Traits: A Review. Front Psychol 2016; 7:1769. [PMID: 27895608 PMCID: PMC5108787 DOI: 10.3389/fpsyg.2016.01769] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Accepted: 10/27/2016] [Indexed: 12/19/2022] Open
Abstract
Schizotypal traits are of interest and importance in their own right and also have theoretical and clinical associations with schizophrenia. These traits comprise attenuated psychotic symptoms, social withdrawal, reduced cognitive capacity, and affective dysregulation. The link between schizotypal traits and psychotic disorders has long since been debated. The status of knowledge at this point is such schizotypal traits are a risk for psychotic disorders, but in and of themselves only confer liability, with other risk factors needing to be present before a transition to psychosis occurs. Investigation of schizotypal traits also has the possibility to inform clinical and research pursuits concerning those who do not make a transition to psychotic disorders. A growing body of literature has investigated the genetic underpinnings of schizotypal traits. Here, we review association, family studies and describe genetic disorders where the expression of schizotypal traits has been investigated. We conducted a thorough review of the existing literature, with multiple search engines, references, and linked articles being searched for relevance to the current review. All articles and book chapters in English were sourced and reviewed for inclusion. Family studies demonstrate that schizotypal traits are elevated with increasing genetic proximity to schizophrenia and some chromosomal regions have been associated with schizotypy. Genes associated with schizophrenia have provided the initial start point for the investigation of candidate genes for schizotypal traits; neurobiological pathways of significance have guided selection of genes of interest. Given the chromosomal regions associated with schizophrenia, some genetic disorders have also considered the expression of schizotypal traits. Genetic disorders considered all comprise a profile of cognitive deficits and over representation of psychotic disorders compared to the general population. We conclude that genetic variations associated with schizotypal traits require further investigation, perhaps with targeted phenotypes narrowed to assist in refining the clinical end point of significance.
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Affiliation(s)
- Emma E. Walter
- School of Psychology, University of WollongongWollongong, NSW, Australia
| | - Francesca Fernandez
- Illawarra Health and Medical Research Institute, University of WollongongWollongong, NSW, Australia
| | - Mollie Snelling
- Illawarra Health and Medical Research Institute, University of WollongongWollongong, NSW, Australia
| | - Emma Barkus
- School of Psychology, University of WollongongWollongong, NSW, Australia
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Xu J, Qin W, Li Q, Li W, Liu F, Liu B, Jiang T, Yu C. Prefrontal Volume Mediates Effect ofCOMTPolymorphism on Interference Resolution Capacity in Healthy Male Adults. Cereb Cortex 2016; 27:5211-5221. [DOI: 10.1093/cercor/bhw301] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Accepted: 09/07/2016] [Indexed: 12/11/2022] Open
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18
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Li R, Ma X, Wang G, Yang J, Wang C. Why sex differences in schizophrenia? JOURNAL OF TRANSLATIONAL NEUROSCIENCE 2016; 1:37-42. [PMID: 29152382 PMCID: PMC5688947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Clinical observation shows that men and women are different in prevalence, symptoms, and responses to treatment of several psychiatric disorders, including schizophrenia. While the etiology of gender differences in schizophrenia is only partially understood, recent genetic studies suggest significant sex-specific pathways in the schizophrenia between men and women. More research is needed to understand the causal roles of sex differences in schizophrenia in order to ultimately develop sex-specific treatment of this serious mental illness. In the present review, we will outline the current evidence on the sex-related factors interaction with disease onset, symptoms and treatment of schizophrenia, and discuss the potential molecular mechanisms that may mediate their cooperative actions in schizophrenia pathogenesis.
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Affiliation(s)
- Rena Li
- Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital Capital Medical University, Beijing 100088, China
- Center of Schizophrenia, Beijing Institute for Brain Disorders, Beijing 100069, China
- Center for Hormone Advanced Science and Education, Roskamp Institute, Sarasota, FL 34243, USA
| | - Xin Ma
- Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital Capital Medical University, Beijing 100088, China
| | - Gang Wang
- Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital Capital Medical University, Beijing 100088, China
| | - Jian Yang
- Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital Capital Medical University, Beijing 100088, China
| | - Chuanyue Wang
- Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital Capital Medical University, Beijing 100088, China
- Center of Schizophrenia, Beijing Institute for Brain Disorders, Beijing 100069, China
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